NGF PROTECTS PC12 CELLS AGAINST ISCHEMIA BY A MECHANISM THAT REQUIRES THE N-KINASE
NGF PROTECTS PC12 CELLS AGAINST ISCHEMIA BY A MECHANISM THAT REQUIRES THE N-KINASE
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DOI：
10.1002/jnr.490400102
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发表时间：
1995-01-01
影响因子：
4.2
通讯作者：
WAGNER, JA
中科院分区：
文献类型：
--
作者：
BONIECE, IR;WAGNER, JA
神经生长因子（NGF）已被证明是PC12细胞的形态学和神经化学分化因子，也保护PC12细胞免受血清戒断和缺血的毒性。通过使用先前建立的体外缺血模型，包括缺氧和葡萄糖剥夺的组合（Boniece和Wagner: J Neurosci: 420 -4228, 1993），我们已经能够研究NGF诱导存活所依赖的信号转导途径。在这里，我们证明了n激酶和NGF诱导的神经生成抑制剂，6-硫鸟嘌呤和2-氨基嘌呤，阻止了NGF的保护作用，而它们对表皮生长因子（EGF）或dbcAMP的保护作用几乎没有影响，这表明只有NGF通过强烈依赖于n激酶的机制起作用，此外，甲基转移酶抑制剂5'-脱氧-5'-甲基硫腺苷（MTA）也抑制NGF诱导的神经生成。因此，NGF的神经保护作用需要一些与NGF促进分化和神经突形成相同的信号转导步骤。此外，我们发现PC12细胞暴露于维甲酸中，可以促进PC12细胞的分化和抑制PC12细胞的生长，也可以提高缺血时的细胞存活率。NGF和维甲酸联合使用比单独使用任何一种药物都更有效，这可能是这两种药物通过独立的途径赋予保护作用。(C) 1995 Wiley-Liss, Inc。
Nerve growth factor (NGF), which has been shown to act as a morphological and neurochemical differentiating factor in PC12 cells, also protects PC12 cells from the toxicity of serum withdrawal and ischemia, By using a previously established in vitro model of ischemia, which incorporates the combination of anoxia with glucose deprivation (Boniece and Wagner: J Neurosci 13:4220-4228, 1993), we have been able to study the signal transduction pathways upon which NGF-induced survival is dependent. Here we demonstrate that inhibitors of the N-kinase and NGF-induced neuritogenesis, 6-thioguanine and 2-aminopurine, prevent the protective effects of NGF, while they have little, if any, effect on the protection conferred by epidermal growth factor (EGF) or dbcAMP, This suggests that only NGF acts by a mechanism that depends strongly on the N-kinase, Furthermore, the methyltransferase inhibitor 5'-deoxy-5'-methylthioadenosine (MTA), which also inhibits NGF-induced neuritogenesis, inhibits the protective effect of NGF but not the protective effects of EGF or dbcAMP, Thus, the neuroprotective effect of NGF requires some of the same signal transduction steps used by NGF to promote differentiation and neurite formation, Furthermore, we found that exposure of PC12 cells to retinoic acid, which promotes the differentiation and inhibits the growth of PC12 cells, also improves cell survival during ischemia, In addition, a combination of NGF and retinoic acid was more effective than either agent alone, It is likely that these two agents confer protection by independent pathways. (C) 1995 Wiley-Liss, Inc.